The present invention relates to a novel process for the production of magaldrate and to the use of the product produced thereby in pharmaceutical products, particularly antacids.
According to United States Pharmacopoeia XXI/1985, First Supplement, USP-NF page 1740, magaldrate is an aluminum magnesium hydroxide sulfate of the formula EQU Al.sub.5 Mg.sub.10 (OH).sub.31 (SO.sub.4).sub.2..times.H.sub.2 O
where x is preferably 0-6,77 (according to United States Pharmacopoeia XXI/1985, but can be also greater than 6,77.
It may be manufactured and used in hydrated as well as dehydrated form and is considered a chemical combination of aluminum hydroxide and magnesium hydroxide. Moreover, it contains not less than 29.0% and not more than 40.0% of the equivalent quantity of MgO and not less than 18% and not more than 26% of the equivalent quantity of Al.sub.2 O.sub.3. With reference to magaldrate that is free of water, the formula yields a theoretical sulfate content of about 17.5%.
The USP standard magaldrate is characterized by having a maximum water soluble sulfate content of 1.9%, and a specific X-ray diffraction spectrum in the range of 0.18 to 2.20 nm, among other features.
Magaldrate is used as the active antacid ingredient in known antacids. The advantageous characteristics of these magaldrate containing antacids, such as fast and long lasting acid neutralization, long-term stability, distinct adsorption capability with respect to pepsin, bile acid and lysolecithin are the result of the composition and structure of magaldrate.
Magaldrate, formerly called magnesium aluminate hydrate, has been produced for a long time. In the method for producing magaldrate according to German Patent Application No. B 36,762 IVa/30 h, a magnesium salt solution is added under intensive mixing to a highly basic alkalialuminate solution containing three to five moles of Na.sub.2 O or another alkali oxide for each mole of Al.sub.2 O.sub.3 at a temperature which does not exceed 50.degree. C. and in such quantities that the ratio of aluminum to magnesium is 1:0.9 to 3. The resulting precipitate is separated from the solution, washed and possibly gently dried. The ratio of aluminum to magnesium employed is preferably 1:2.
Although in the examples of the above-described reference magnesium sulfate is used exclusively, the process is not limited to this magnesium salt. Obviously, for this reason magaldrate was not formulated as a sulfate containing compound in the German patent application or in earlier U.S. Pharmacopoeae.
Using the process of German Patent Application No. B 36,762 IVa/30h at an atomic ratio of Mg:Al of 2:1, only after thoroughly washing the filter cake is magaldrate of the stated formula obtained. After washing with water, the filter cake can be homogenized into a paste and can be processed, with the addition of preservatives, flavoring agents and other adjuvants, to produce a liquid antacid preparation. Alternatively, the washed filter residue or the paste can be dried and used as the active antacid ingredient in the manufacture of antacid tablets or powders.
Surprisingly, it has now been discovered that the prior art method can be replaced by a novel, significantly better method. Precipitation, filtration and, particularly, washing are known to be time consuming and are, therefore, operations which reduce production capacity in the prior art process, and considerably increase the manufacturing costs compared to processes for the manufacture of other active antacid substances, such as aluminum hydroxide gel and aluminum phosphate gel. For example, a washing time of about 200 minutes is required to wash aluminum hydroxide gel produced according to the process of German Patent No. 1,921,999 in a 100 m.sup.2 filter press. However, magaldrate produced according to the above-cited German patent application requires about four times the amount of time, i.e. approximately 800 minutes.
A further drawback of this prior art process is that filter cake concentrations of only about 10 to 13 weight percent magaldrate can be obtained with present-day filtration techniques employing rotary filters or filter presses. Consequently, in the subsequent formulation, only those end products whose magaldrate concentration lies slightly below this concentration range can be obtained. Accordingly, the liquid antacids containing magaldrate that are presently commercially available comprise only 9 weight percent magaldrate, on the average.